The potential protective effect of aqueous extract of Acanthophyllum glandulosum root on Streptozotocin-induced diabetes in mice.

Purpose: Treatment of diabetes using traditional medicine has attracted attention in recent decades because of its unique benefits. Acanthophyllum glandulosum is known as an herb with therapeutic potential. This research explored the likely protective effects of Acanthophyllum Glandulosum Root (AGR) in mice with Streptozotocin-induced type 2 diabetes mellitus (T2DM) to provide complementary therapy. Methods: Diabetes was induced by a single injection of Streptozotocin (STZ) in mice. STZ-diabetic mice were treated with oral dosages of AGR (25, 50, 100, and 200 mg/kg) on different experiment days. During the experiment, the effect of a topical extract of AGR on Glucose level, serum lipid profile, and liver and kidney biomarkers, with the histopathological assessment of heart, kidney, spleen, and liver, were investigated. The gene expression level of inflammation biomarkers (Tumour Necrosis Factor-alpha (TNF-α) and interleukin-1 (IL-1)), apoptosis factor (Caspase3), glucose regulatory genes (Glucose transporter (GLUT) 4 and 2), and lipid regulatory gene (Adenosine 50-monophosphate protein-kinase (AMPK)) were investigated. Results: Administration of AGR to STZ-diabetic mice decreased blood glucose level (p < 0.01), normalized the lipid profile (p < 0.01), improved the serum level of kidney (p < 0.01) and liver biomarkers (p < 0.01), and normalized Kidney hypertrophy (p < 0.01), inflammation (p < 0.001), and apoptosis (p < 0.01). The AGR effect was better at 100 mg/kg than Metformin (100 mg/kg) on healing T2DM condition in mice. Conclusion: AGR possesses anti-inflammatory, antioxidant, anti-hyperglycemic, anti-hyperlipidemic, and anti-glycation activity, thus exhibiting a protective function in STZ-induced diabetic mice. Further in vitro and in vivo works are necessary, especially to elucidate the mechanism of action of AGR at the cellular and molecular levels.

Cyanidin 3-glycoside induced apoptosis in MCF-7 breast cancer cell line.

Introduction: Breast cancer is the major leading cause of death from cancer among women. Given the drug resistance seen during the treatment of this disease, it is very important to identify new therapies and new anticancer drugs. Some studies indicate the cytotoxic effects of cyanidin 3-glycoside (C3G). Therefore, this study aims to evaluate the anticancer effect of C3G in the treatment of the MCF-7 cell line. Material and methods: In this study, the MCF-7 cell line was treated with different concentrations of C3G for 24 and 48 h. Assessment of cell death was performed by MTT assay. The cell apoptosis rate was measured using an Annexin V/propidium iodide assay through flow cytometry. The expression levels of p53, Bax, Caspase3, CYP1, CYP2, and Bcl2 genes were evaluated using polymerase chain reaction, and Western blotting was performed for CYP1 to confirm the results. Results: Our findings showed that C3G has dose-dependent cytotoxic effects on the MCF-7 cell line. According to flow cytometry results, the apoptosis of the cells 24 h after exposure to C3G was more than 51.5%. Moreover, after 24 h of exposure to the half-maximal inhibitory concentration of C3G, the expression of p53, Bax, Caspase3, CYP1, and CYP2 genes increased, and the expression of Bcl2 gene decreased. The Western blotting showed that CYP1 protein increased 2-fold compared to the control sample. Conclusions: The results of this study demonstrated that C3G has apoptotic and cytotoxic effects on breast cancer cells. Therefore, it is likely that this substance could be a suitable option for cancer therapy.

Role of curcumin and its nanoformulations in the treatment of neurological diseases through the effects on stem cells.

Curcumin from turmeric is a natural phenolic compound with a promising potential to regulate fundamental processes involved in neurological diseases, including inflammation, oxidative stress, protein aggregation, and apoptosis at the molecular level. In this regard, employing nanoformulation can improve curcumin efficiency by reducing its limitations, such as low bioavailability. Besides curcumin, growing data suggest that stem cells are a noteworthy candidate for neurodegenerative disorders therapy due to their anti-inflammatory, anti-oxidative, and neuronal-differentiation properties, which result in neuroprotection. Curcumin and stem cells have similar neurogenic features and can be co-administered in a cell-drug delivery system to achieve better combination therapeutic outcomes for neurological diseases. Based on the evidence, curcumin can induce the neuroprotective activity of stem cells by modulating their related signalling pathways. The present review is about the role of curcumin and its nanoformulations in the improvement of neurological diseases alone and through the effect on different categories of stem cells by discussing the underlying mechanisms to provide a roadmap for future investigations.

Hypericin induces apoptosis in K562 cells via downregulation of Myc and Mdm2.

BACKGROUND: Nowadays, some studies have shown the effect of hypericin on cancer cells. However, considering the cytotoxicity of this plant and signs of anticancer activity in the plant, unfortunately, there is still no proper treatment for leukemia cancer cells. Therefore, the present study aims to evaluate the anticancer effect of hypericin in the treatment of leukemia cancer and its possible mechanism of action. METHODS: In this study, the K562 cell line was treated with different concentrations of hypericin for 24 and 48 h. Detection of cell death was performed by 3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl-2-tetrazolium bromide assay. The rate of cell apoptosis was measured by Annexin V/propidium iodide assay using flow cytometry. The expression of Bax, Bcl2, Myc, Mdm2, and P53 genes was evaluated by real-time polymerase chain reaction test, and immunocytochemistry (ICC) analysis was used for further evaluation of P53. RESULTS: The results showed that hypericin has a dose-dependent cytotoxic effect on the K562 (in much less dose compared with cisplatin). According to flow cytometry results, cell apoptosis after exposure to hypericin for 24 h was 53%, and ICC analysis on p53 confirmed this. Furthermore, after 24 h of exposure to hypericin with IC50 concentration, the expression of P53 and Bax genes increased and the expression of the Bcl2, Myc, and Mdm2 gene decreased. CONCLUSION: The results showed that hypericin exerts its cytotoxicity on K562 cancer cells by downregulating Mdm2 and Myc. Based on the data acquired from the present study and many investigations till now, hypericin can be a good option for leukemia cancer cells treatment.

A significant association between CXCL10 -1447 A > G and IL18 -607 C > A gene polymorphism with human T-cell lymphotropic virus type 1 associated myelopathy/tropical spastic paraparesis (HAM-TSP), a case-control report from city of Mashhad, Iran.

Human T-cell lymphotropic virus type 1 (HTLV-1) is the first isolated retrovirus from humans, and 2-3% of infected individuals suffer from HTLV-1 associated myelopathy tropical spastic paraparesis (HAM-TSP). Previous studies indicated that the risk of HAM-TSP could be correlated with the individuals' genetic alterations. Mashhad is one of the areas infected with HTLV-1 in Iran. This study designed to examine the association between several important gene polymorphisms and HAM-TSP. Genotypes of 232 samples from controls, HTLV-1 carriers, and HAM-TSP patients were examined for FAS-670 (A > G), CXCL10-1447 (A > G), Foxp3-3279 (C > A), IL-18 -137 (C > G), and IL-18 -607 (C > A) gene polymorphisms by different polymerase chain reaction (PCR) techniques. A non-significant association was observed between FAS-670 A > G, Foxp3-3279 C > A, and IL-18 -137 C > G gene polymorphisms and HAM-TSP. Nevertheless, a significant (P < 0.001) association between CXCL10-1447 A > G and IL-18 -607 C > A gene polymorphisms with HAM-TSP was observed in our study population. As previous studies revealed that the CXCL10 level in the cerebrospinal fluid of HAM-TSP patients was associated with the disease progression, and as we noticed, a direct association was observed between CXCL10-1447 A > G polymorphism and HAM-TSP. These polymorphisms might be recommended as a valuable prediction criterion for the severity of the disease. The contradiction between our findings and other studies regarding IL-18 -607 C > A gene polymorphism might be associated with various factors such as genotypes frequency in diverse races and population heterogeneity in the city of Mashhad.

Monocytes and macrophages in COVID-19: Friends and foes.

The COVID-19 is a novel infectious disease caused by SARS-CoV-2 and is known as a pandemic emergency that has led to a high rate of mortality throughout the world. Evidence has indicated that hyperinflammatory responses triggered by SARS-CoV-2 are the main cause of pathogenicity in the severe cases of patients who have died during the current viral disease. Monocytes and macrophages as the most important cells of the innate arm of the immune system play a substantial part in the body's defense against viral infections. They mainly respond to the microbial antigens by producing inflammatory mediators to remove pathogens and repair tissue injury. Nevertheless, aberrant alterations in their function such as cytokine storm can be so harmful to the host in the acute respiratory distress syndrome cases caused by SARS-CoV-2. Moreover, inflammatory responses stimulated by SARS-CoV-2 have affected the other vital organs of the body including the heart. As cardiovascular complications in COVID-19 patients have been reported in several studies. During the infection, monocytes and macrophages may be involved in the hypersensitive and exacerbated reactions that contribute to the tissue damage, especially lung injury resulted in its dysfunction and respiratory disorder. In this review, we discuss both advantageous and disadvantageous about the pathological potential of monocytes and macrophages during the infection of SARS-CoV-2 to clarify their mutual effects on immune processing as a fist line defender in the current disease.

Ginger (Zingiber Officinale Roscoe) Extract Protects the Heart Against Inflammation and Fibrosis in Diabetic Rats.

BACKGROUND: Fibrosis and inflammation in the heart of patients with diabetes mellitus alongside increased production of free radicals and collagen are together known as diabetic cardiomyopathy. Ginger rhizome has antidiabetic, antioxidant and anti-inflammatory effects. Thus, we investigated the effect of ginger extract on diabetes-induced cardiomyopathy in streptozotocin-induced diabetic rats. METHODS: Animals were divided into 7 groups: control; diabetic; diabetic treated with different doses of ginger extract of 100, 200 and 400 mg/kg; metformin (200 mg/kg); and metformin-valsartan (200 and 30 mg/kg, respectively). Serum levels of glucose, aspartate aminotransferase, lactate dehydrogenase and creatine kinase-muscle/brain were measured. Fibrosis and inflammation were determined by histologic assessment. Gene expression of transforming growth factor (TGF)-ß1, TGF-ß3 and angiotensin II type 1 receptor was evaluated by real-time polymerase chain reaction in heart tissue. RESULTS: Serum glucose level in all treated groups, except for the ginger extract 100-mg/kg group, was significantly lower than in the diabetic group. Serum levels of aspartate aminotransferase, lactate dehydrogenase and creatine kinase-muscle/brain were significantly reduced in all treated groups compared with the diabetic group. In the study of fibrosis, collagen amount in the heart tissue of all treated groups, except the ginger extract 100-mg/kg group, was significantly lower than in the diabetic group. Inflammatory cell infiltrates were decreased, and disarrangement was improved in cardiac tissues of all treated groups compared with the diabetic group. Expression of angiotensin II type 1 receptor and TGF-ß1 and TGF-ß3 genes in all treated groups downregulated compared with the diabetic group. CONCLUSIONS: Treatment by ginger extract reduced myocardial fibrosis and inflammation in the course of diabetic cardiomyopathy, possibly through regulation of the expression of genes involved in the SMAD/TGF-ß pathway.

Gene expression pattern of CCL2, CCL3, and CXCL8 in patients with bipolar disorder.

BACKGROUND: Bipolar disorder (BD) is one of the most important psychiatric disorders in the world. There is evidence suggesting the role of inflammatory mediators such as chemokines in the etiology of BD. The objective of the current study was to evaluate the gene expression of CCL2, CCL3, and CXCL8 in patients with BD and compare them to healthy controls. MATERIALS AND METHODS: A total of 48 patients with confirmed BD and 48 healthy controls enrolled in this study. All patients were recruited from April to August 2016 at Ibn-Sina Psychiatric Hospital, Mashhad University of Medical Sciences, Mashhad, Iran. RNA was extracted from the whole blood samples and then cDNA was synthesized. Gene expression of CCL2, CCL3, and CXCL8 was measured using SYBR® Green real-time polymerase chain reaction. The difference of delta-CT values between patients and healthy controls was compared with the independent samples t-tests. RESULTS: CCL2 and CXCL8 genes expressed at higher levels in patients with BD as compared to healthy controls, but not significant. On the contrary, we found lower expression levels for CCL3 gene in our patients compared to healthy controls, but the difference was not statistically significant. CONCLUSION: Our findings do not show an association between the gene expression of CCL2, CCL3 and CXCL8 and BD. Increasing the sample size and evaluation on the gene expression of other chemokines in depression and mania phases of BD might be helpful to get a better conclusion.

Improved chondrogenic response of mesenchymal stem cells to a polyethersulfone/polyaniline blended nanofibrous scaffold.

Owing to the fact that the cartilage tissue is not able to repair itself, the treatment of the joint damages is very difficult by current methods. Induction of tissue repair requires suitable cell and extracellular matrix. Providing these two parts can only be done using tissue engineering. In the present study, polyethersulfone (PES) and polyaniline (PANI) blend was electrospined for nanofibrous scaffold fabrication. Mesenchymal stem cells were isolated from human adipose tissue (AT-MSCs), and after characterization cultured on the PES-PANI scaffold and culture plate. Electron microscopic and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assays were used for biocompatibility evaluation of the scaffold and the chondrogenic differentiation potential of AT-MSCs were investigated by staining of proteoglycans and gene and protein expression evaluation. Alcian blue staining, real-time reverse-transcriptase polymerase chain reaction and Western blot results showed that chondrogenic differentiation potential of AT-MSCs was significantly increased when grown on PES-PANI nanofibers and was compared to the one grown on a culture plate. According to the results, PES-PANI has a promising potential to be used as a biomedical implant in patients with joints lesion, such as arthritis and osteoarthritis.

Poly (3-hydroxybutyrate-co-3-hydroxyvalerate) improved osteogenic differentiation of the human induced pluripotent stem cells while considered as an artificial extracellular matrix.

Cocell polymers can be the best implants for replacing bone defects in patients. The pluripotent stem cells produced from the patient and the nanofibrous polymeric scaffold that can be completely degraded in the body and its produced monomers could be also usable are the best options for this implant. In this study, electrospun poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanofibers were fabricated and characterized and then osteogenic differentiation of the human-induced pluripotent stem cells (iPSCs) was investigated while cultured on PHBV scaffold. MTT results showed that cultured iPSCs on PHBV proliferation were increased compared to those cultured on tissue culture polystyrene (TCPS) as the control. Alkaline phosphatase (ALP) activity and calcium content were also significantly increased in iPSCs cultured on PHBV compared to the cultured on TCPS under osteogenic medium. Gene expression evaluation demonstrated that Runx2, collagen type I, ALP, osteonectin, and osteocalcin were upregulated in iPSCs cultured on PHBV scaffold in comparison with those cultured on TCPS for 2 weeks. Western blot analysis have shown that osteocalcin and osteopontin expression as two major osteogenic markers were increased in iPSCs cultured on PHBV scaffold. According to the results, nanofiber-based PHBV has a promising potential to increase osteogenic differentiation of the stem cells and iPSCs-PHBV as a cell-co-polymer construct demonstrated that has a great efficiency for use as a bone tissue engineered bioimplant.

Effect of Hydroalcoholic Extract of Rosmarinus officinalis L. Leaf on Anxiety in Mice.

In today's stressful world, psychopathy (especially anxiety) is receiving increased importance. Most of the drugs used to treat this disease have several side effects. Medicinal plants derived from natural products have fewer side effects and can be used in the treatment of this disease. The aim of this study was to evaluate the effect of the hydroalcoholic extract of Rosmarinus officinalis L. on anxiety in mice. In this experimental study, 50 male mice were randomly divided into 5 groups. To evaluate anxiety, the Elevated Plus Maze test was performed. The control group received normal saline, the positive control group received diazepam (1 mg/kg) as intraperitoneal injection, and the experimental groups received doses of 100, 200, and 400 mg/kg body weight of rosemary extract. The data were analyzed using SPSS 15 and ANOVA statistical tests. The results show that rosemary extract dose-dependently increases the mice spending time and the entries number of mice in plus maze open arms (indicating less stress). This effect at a dose of 400 mg/kg was similar to diazepam, which, in comparison to the control group, was statistically significant (P < .01), while the evaluation of locomotor activity in treated groups, compared with the control groups, showed no significant difference (P > .05). On the other hand, the rosemary extract, similar to the standard drug diazepam, showed an anti-anxiety effect. This effect is probably due to the presence of flavonoids in this plant and their antioxidant property.